HealthyPhase 1NCT02617810
A Study to Assess the Effect of Multiple-Dose Administration of JNJ-42847922 on Midazolam and Warfarin in Healthy Participants
A Phase 1 study testing JNJ-42847922, Midazolam and Warfarin in people with Healthy, run by Janssen Research & Development, LLC at 1 site in United States.
Trial summary
The purpose of this study is to evaluate effect of multiple-dose administration of JNJ-42847922 on the single-dose pharmacokinetics of oral midazolam and single-dose pharmacokinetics and pharmacodynamics of (R)- and (S)-warfarin after oral administration of racemic warfarin. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- JNJ-42847922, Midazolam and Warfarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
- Willing to adhere to the prohibitions and restrictions specified in protocol
- If a woman, must be not of child-bearing potential: postmenopausal [greater than or equal to (>=) 45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum stimulating hormone (FSH) greater than (>) 40 International units per liter (IU/L), or surgically sterile (example, hysterectomy, oophorectomy, tubal ligation or tubal occlusion)
- If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction for at least 3 months after the last dose of study drug
- If a man who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator (example, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
- Body mass index (BMI) between 18 and 30 kilogram (kg)/meter^2 (m^2), and body weight not less than 50 kg
Who cannot join
- History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), syncope, hypotension, hypertension or vascular disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, kidney or urinary tract disturbances, thyroid disease, neurologic disease, significant psychiatric disorder, epilepsy, or fits of unexplained black-outs, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- Clinically significant abnormal values for hematology, clinical chemistry, urinalysis, or thyroid stimulating hormone (TSH) at Screening or at Day -1 of the first treatment period as deemed appropriate by the Investigator. In addition, participants must have coagulation test results [(prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT)] within clinically acceptable limits at Screening as deemed appropriate by the Investigator
- Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or Day -1 of the first treatment period as deemed appropriate by the Investigator
- Participants who are homozygous or heterozygous for CYP2C9*2 or CYP2C9*3 alleles
- Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, within 14 days before the first dose of the study drug is scheduled until completion of the study. In addition, participants will be excluded if they have used medications known to affect coagulation or modulate CYP2C9 or VKORC1 within 28 days of study admission
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label Drug Interaction Study to Assess the Effect of Multiple-Dose Administration of JNJ-42847922 on the Single-Dose Pharmacokinetics of Midazolam and the Single Dose Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects
The purpose of this study is to evaluate effect of multiple-dose administration of JNJ-42847922 on the single-dose pharmacokinetics of oral midazolam and single-dose pharmacokinetics and pharmacodynamics of (R)- and (S)-warfarin after oral administration of racemic warfarin.
Read the detailed description
This is an open-label (all people know the identity of the intervention), single-center, fixed-sequence, study of JNJ-42847922 in healthy participants. The study consists of 3 Phases: Screening Phase (28 Days), open-label treatment Phase (40 Days) and follow up visit (7 to 14 Days after last study procedure). The duration of participation in the study for each participant is approximately 82 Days. Participants' safety will be monitored throughout the study.
- Conditions
- Healthy
- Keywords
- Healthy, JNJ-42847922, Midazolam, Warfarin, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-42847922Drug
Participants will receive JNJ-42847922 20 milligram (mg) tablet orally once daily from Day 1 to Day 9.
MidazolamDrug
Participants will receive midazolam 4 milligram (mg) syrup orally once on Day 1 during treatment A and on Day 7 during treatment B.
WarfarinDrug
Participants will receive warfarin 25 milligram (mg) tablet orally once on Day 3 during treatment A and on Day 9 during treatment B.
| Study group | Role | What they receive |
|---|---|---|
| JNJ-42847922 Plus Midazolam Plus Warfarin | Experimental | Participants will receive Treatment A (midazolam 4 milligram [mg] syrup once on Day 1 and warfarin 25 mg tablet once on Day 3) followed by Treatment B (JNJ-42847922 20 mg once daily from Day 1 to Day 9, midazolam 4 mg syrup once on Day 7 and warfarin 25 mg tablet once on Day 9). A washout period of 14 to 21 days will be maintained between each treatment period. Receives: Drug: JNJ-42847922; Drug: Midazolam; Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax) of Midazolam
The Cmax is the maximum observed plasma concentration of Midazolam.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Maximum Plasma Concentration (Cmax) of 1-Hydroxymidazolam
The Cmax is the maximum observed plasma concentration of 1-Hydroxymidazolam.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Maximum Plasma Concentration (Cmax) of Warfarin
The Cmax is the maximum observed plasma concentration of Warfarin.
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Time to Reach the Maximum Plasma Concentration (Tmax) of Midazolam
The Tmax is the time to reach the maximum observed plasma concentration of Midazolam.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Time to Reach the Maximum Plasma Concentration (Tmax) of 1-Hydroxymidazolam
The Tmax is the time to reach the maximum observed plasma concentration of 1-Hydroxymidazolam.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Time to Reach the Maximum Plasma Concentration (Tmax) of Warfarin
The Tmax is the time to reach the maximum observed plasma concentration of Warfarin.
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Time of Last Measurable Plasma Concentration (Tlast) of Midazolam
Time to last measurable plasma concentration is evaluated.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Time of Last Measurable Plasma Concentration (Tlast) of 1-Hydroxymidazolam
Time to last measurable plasma concentration is evaluated.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Time of Last Measurable Plasma Concentration (Tlast) of Warfarin
Time to last measurable plasma concentration is evaluated.
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of Midazolam
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of 1-Hydroxymidazolam
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of Warfarin
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Midazolam
The AUC (0-infinity) is the area under the plasma Midazolam concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Midazolam concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of 1-Hydroxymidazolam
The AUC (0-infinity) is the area under the plasma 1-Hydroxymidazolam concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma 1-Hydroxymidazolam concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Warfarin
The AUC (0-infinity) is the area under the plasma Warfarin concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Warfarin concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Terminal Half-life (t[1/2]) of Midazolam
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Terminal Half-life (t[1/2]) of 1-Hydroxymidazolam
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Terminal Half-life (t[1/2]) of Warfarin
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Total Apparent Clearance (CL/F) of Midazolam
The CL/F is defined as Dose/AUC (0-infinity).
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Total Apparent Clearance (CL/F) of 1-Hydroxymidazolam
The CL/F is defined as Dose/AUC (0-infinity).
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Total Apparent Clearance (CL/F) of Warfarin
The CL/F is defined as Dose/AUC (0-infinity).
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Apparent Volume of Distribution (Vd/F) of Midazolam
The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Apparent Volume of Distribution (Vd/F) of 1-Hydroxymidazolam
The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
Measured: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Apparent Volume of Distribution (Vd/F) of Warfarin
The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Maximum Observed Effect (Emax) for Prothrombin Time (PT)
The Emax for prothrombin time (PT) will be assessed.
Measured: Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Maximum Observed Effect (Emax) for activated Partial Thromboplastin Time (aPTT)
The Emax for activated partial thromboplastin time (aPTT) will be assessed.
Measured: Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Maximum Observed Effect (Emax) for International Normalized Ratio (INR)
The Emax for international normalized ratio (INR) will be assessed.
Measured: Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-42847922
The Tmax is the time to reach the maximum observed plasma concentration of JNJ-42847922.
Measured: 2 hours postdose on Day 1 to Day 6; 2 and 26 hours postdose on Day 7; 2 hours postdose on Day 9 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to 168 Hours (AUC[0-168]) Post Dose of Warfarin
The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.
Measured: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Area Under the Plasma Concentration-Time Curve From 0 to 168 Hours (AUC[0-168]) Post Dose of JNJ-42847922
The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.
Measured: 2 hours postdose on Day 1 to Day 6; 2 and 26 hours postdose on Day 7; 2 hours postdose on Day 9 during Treatment B
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Measured: Day -1 of Treatment A dosing
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Measured: 4 hours postdose on Day 1 during Treatment A
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Measured: 8 hours postdose on Day 1 during Treatment A
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Measured: Day -1 of Treatment B dosing
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Measured: 4 hours postdose on Day 7 during Treatment B
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Measured: 8 hours postdose on Day 7 during Treatment B
Secondary outcomes (1)
Number of Participants with Adverse Events (AEs) and Serious AEs
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measured: Screening up to follow-up visit (7 to 14 days after last study procedure)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2015 (estimated)
- Study startNov 2015
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02617810
- Sponsor's protocol ID
- CR108066
- Other IDs
- 42847922EDI1010
- Status last verified
- Feb 2016
- First submitted
- 13 Nov 2015
- Last updated
- 23 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Drug Interaction Study to Assess the Effect of Multiple-Dose Administration of JNJ-42847922 on the Single-Dose Pharmacokinetics of Midazolam and the Single Dose Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02617810
- Acronym / sponsor ID
- CR108066
- Conditions
- Healthy
- Keywords
- Healthy, JNJ-42847922, Midazolam, Warfarin, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- Nov 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 1 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate effect of multiple-dose administration of JNJ-42847922 on the single-dose pharmacokinetics of oral midazolam and single-dose pharmacokinetics and pharmacodynamics of (R)- and (S)-warfarin after oral administration of racemic warfarin.
Detailed description
This is an open-label (all people know the identity of the intervention), single-center, fixed-sequence, study of JNJ-42847922 in healthy participants. The study consists of 3 Phases: Screening Phase (28 Days), open-label treatment Phase (40 Days) and follow up visit (7 to 14 Days after last study procedure). The duration of participation in the study for each participant is approximately 82 Days. Participants' safety will be monitored throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| JNJ-42847922 Plus Midazolam Plus Warfarin | Experimental | Drug: JNJ-42847922, Drug: Midazolam, Drug: WarfarinParticipants will receive Treatment A (midazolam 4 milligram [mg] syrup once on Day 1 and warfarin 25 mg tablet once on Day 3) followed by Treatment B (JNJ-42847922 20 mg once daily from Day 1 to Day 9, midazolam 4 mg syrup once on Day 7 and warfarin 25 mg tablet once on Day 9). A washout period of 14 to 21 days will be maintained between each treatment period. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
- Willing to adhere to the prohibitions and restrictions specified in protocol
- If a woman, must be not of child-bearing potential: postmenopausal [greater than or equal to (>=) 45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum stimulating hormone (FSH) greater than (>) 40 International units per liter (IU/L), or surgically sterile (example, hysterectomy, oophorectomy, tubal ligation or tubal occlusion)
- If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction for at least 3 months after the last dose of study drug
- If a man who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator (example, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
Key exclusion criteria (5 listed)
- History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), syncope, hypotension, hypertension or vascular disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, kidney or urinary tract disturbances, thyroid disease, neurologic disease, significant psychiatric disorder, epilepsy, or fits of unexplained black-outs, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- Clinically significant abnormal values for hematology, clinical chemistry, urinalysis, or thyroid stimulating hormone (TSH) at Screening or at Day -1 of the first treatment period as deemed appropriate by the Investigator. In addition, participants must have coagulation test results [(prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT)] within clinically acceptable limits at Screening as deemed appropriate by the Investigator
- Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or Day -1 of the first treatment period as deemed appropriate by the Investigator
- Participants who are homozygous or heterozygous for CYP2C9*2 or CYP2C9*3 alleles
- Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, within 14 days before the first dose of the study drug is scheduled until completion of the study. In addition, participants will be excluded if they have used medications known to affect coagulation or modulate CYP2C9 or VKORC1 within 28 days of study admission
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JNJ-42847922Participants will receive JNJ-42847922 20 milligram (mg) tablet orally once daily from Day 1 to Day 9. | Drug | JNJ-42847922 Plus Midazolam Plus Warfarin |
| MidazolamParticipants will receive midazolam 4 milligram (mg) syrup orally once on Day 1 during treatment A and on Day 7 during treatment B. | Drug | JNJ-42847922 Plus Midazolam Plus Warfarin |
| WarfarinParticipants will receive warfarin 25 milligram (mg) tablet orally once on Day 3 during treatment A and on Day 9 during treatment B. | Drug | JNJ-42847922 Plus Midazolam Plus Warfarin |
Primary outcome
Maximum Plasma Concentration (Cmax) of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The Cmax is the maximum observed plasma concentration of Midazolam.
Maximum Plasma Concentration (Cmax) of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The Cmax is the maximum observed plasma concentration of 1-Hydroxymidazolam.
Maximum Plasma Concentration (Cmax) of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The Cmax is the maximum observed plasma concentration of Warfarin.
Time to Reach the Maximum Plasma Concentration (Tmax) of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The Tmax is the time to reach the maximum observed plasma concentration of Midazolam.
Time to Reach the Maximum Plasma Concentration (Tmax) of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The Tmax is the time to reach the maximum observed plasma concentration of 1-Hydroxymidazolam.
Time to Reach the Maximum Plasma Concentration (Tmax) of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The Tmax is the time to reach the maximum observed plasma concentration of Warfarin.
Time of Last Measurable Plasma Concentration (Tlast) of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Time to last measurable plasma concentration is evaluated.
Time of Last Measurable Plasma Concentration (Tlast) of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Time to last measurable plasma concentration is evaluated.
Time of Last Measurable Plasma Concentration (Tlast) of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Time to last measurable plasma concentration is evaluated.
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The AUC (0-infinity) is the area under the plasma Midazolam concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Midazolam concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The AUC (0-infinity) is the area under the plasma 1-Hydroxymidazolam concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma 1-Hydroxymidazolam concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The AUC (0-infinity) is the area under the plasma Warfarin concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Warfarin concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Terminal Half-life (t[1/2]) of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Terminal Half-life (t[1/2]) of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Terminal Half-life (t[1/2]) of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Total Apparent Clearance (CL/F) of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The CL/F is defined as Dose/AUC (0-infinity).
Total Apparent Clearance (CL/F) of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The CL/F is defined as Dose/AUC (0-infinity).
Total Apparent Clearance (CL/F) of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The CL/F is defined as Dose/AUC (0-infinity).
Apparent Volume of Distribution (Vd/F) of Midazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
Apparent Volume of Distribution (Vd/F) of 1-Hydroxymidazolam
Time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B
The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
Apparent Volume of Distribution (Vd/F) of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
Maximum Observed Effect (Emax) for Prothrombin Time (PT)
Time frame: Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The Emax for prothrombin time (PT) will be assessed.
Maximum Observed Effect (Emax) for activated Partial Thromboplastin Time (aPTT)
Time frame: Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The Emax for activated partial thromboplastin time (aPTT) will be assessed.
Maximum Observed Effect (Emax) for International Normalized Ratio (INR)
Time frame: Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The Emax for international normalized ratio (INR) will be assessed.
Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-42847922
Time frame: 2 hours postdose on Day 1 to Day 6; 2 and 26 hours postdose on Day 7; 2 hours postdose on Day 9 during Treatment B
The Tmax is the time to reach the maximum observed plasma concentration of JNJ-42847922.
Area Under the Plasma Concentration-Time Curve From 0 to 168 Hours (AUC[0-168]) Post Dose of Warfarin
Time frame: Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B
The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.
Area Under the Plasma Concentration-Time Curve From 0 to 168 Hours (AUC[0-168]) Post Dose of JNJ-42847922
Time frame: 2 hours postdose on Day 1 to Day 6; 2 and 26 hours postdose on Day 7; 2 hours postdose on Day 9 during Treatment B
The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
Time frame: Day -1 of Treatment A dosing
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
Time frame: 4 hours postdose on Day 1 during Treatment A
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
Time frame: 8 hours postdose on Day 1 during Treatment A
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
Time frame: Day -1 of Treatment B dosing
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
Time frame: 4 hours postdose on Day 7 during Treatment B
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)
Time frame: 8 hours postdose on Day 7 during Treatment B
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
1 secondary outcome
Number of Participants with Adverse Events (AEs) and Serious AEs
Time frame: Screening up to follow-up visit (7 to 14 days after last study procedure)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2016.
Related trials for Healthy
RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Recruiting
Effects of Urolithin A Supplementation on Glucose Metabolism in Healthy Adults 55 >= Years Old: A Randomized Triple-Masked Controlled Clinical Trial
Healthy Volunteer
Active, not recruitingPhase 3
A Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of VAX-31 With Influenza Vaccine in Adults ≥ 50 Years of Age
Pneumococcal Disease
Recruiting
Effect of a Fermented Dairy Protein With Prebiotic Fiber on GI Complaints
Digestive Health, Quality of Life
Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JNJ-42847922, Midazolam and Warfarin in people with Healthy, run by Janssen Research & Development, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Plasma Concentration (Cmax) of Midazolam (time frame: Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B). The study lists 36 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2016.